Manufacturing equipment, qualification

Sec. 820.70 Production and process controls - Address production procedures and process controls, changes to the process, environmental controls, clothing and hygiene of personnel, prevention of contamination, suitability and layout of buildings, equipment qualification, maintenance, periodic inspection, and adjustment, removal of unwanted manufacturing materials from devices and automated (computer controlled) processes... 

When new equipment is purchased or there is a change in the manufacturing site, qualification exercises are performed as part of the validation process. Qualification (installation qualification, operation qualification, and performance qualification) for any equipment or facility is an extreme process which involves testing, verification, and documentation to assure that the particular equipment or facility is per the specification and meets the appropriate standards as defined by vendor and required by manufacturing and engineering personnel [14]. 

Running these in series and in parallel, much time can be conserved. The three stages with respect to equipment qualification are sometimes referred to as Equipment Validation, comprising IQ, which ensures that a piece of equipment has been correctly calibrated and installed in accordance with the equipment manufacturer s recommendations (proper voltage, amperage, clearance from wall, exhaust requirements, etc.). It is important to understand that IQ is also required for all utility systems. In most instances, once... 

The transdermal manufacturing process is typically validated after the equipment qualification steps have been successfully completed. A good process validation requires each of the preceding validation steps be done successfully. Given that they are successfully completed, the full-scale process for manufacturing the transdermal is run three consecutive times. All formal SOPs (production, laboratory, warehouse, etc.) that affect the transdermal product must therefore be effective and referenced throughout process-validation activities. 

Equipment Qualification (EQ) is a useful endeavor when the lyophilizer is a complex and sophisticated system. Large-scale manufacturing units commonly include multiple automated support operations. These may include steam-in-... 

In the case of a computer system applied to a live manufacturing process and integral with plant equipment and the process itself, the project validation plan should specify the relationship of the computer system qualification activities and documentation with that of the corresponding plant equipment qualification and process validation. Indeed, the qualification activities and documentation of these elements of a computerized operation are sometimes combined. 

Qualification activities are usually undertaken in order to characterize a facility s services and utilities as well as the equipment that would be used as part of a manufacturing process. As indicated earlier, these activities will include installation and operational activities as part of the validation function. Most companies will issue a report that documents the features of the facility s processing rooms, such as the electrical, water, gas, and HVAC services, for the installation qualification. Table 5 is a generic outline of the items that would be found in the IQ report. Whenever the process equipment is permanendy fixed in these rooms, the report will also list the equipment as well as its operating requirements and features. See Table 6 for an outline of questions that would be used to complete a report, which includes equipment qualification. It is preferred that qualification occur as soon as the equipment or facility is ready for routine operation so that any unexpected results will be corrected by the equipment vendor and/or construction contractor. 

The approval of the qualification reports provides confirmation that the computer system as a whole is fit for its purpose, and that all essential documentation is available. For computer systems controlling manufacturing equipment (e.g., process control systems), the approval of the qualification reports indicate that the computerized systems is released for Process/Product Performance Qualification. On other computer systems, the approval of the reports releases the system to the user. 

Note This activity is the culmination of computer systems controlling manufacturing equipment and is out of the scope of computer systems validation. This qualification may be performed by QA or R D and only on manufacturing systems. 

It is essential that the validation program is documented and that the documentation is properly maintained. Approval and release of the process for use in routine manufacturing should be based upon a review of all the validation documentation, including data from the equipment qualification, process performance qualification and product/package testing to ensure compatibility with the process. 

Observation— The firm failed to complete an equipment qualification (IQ/OQ) for their new encapsulation machine prior to use. The firm lacked data to assure that this encapsulation machine was installed and working correctly per manufacturer s specifications. ... 

A fimdamental requirement of Good Analytical Chemistry is that the analytical equipment should be suitable for the intended use and should be cahbrated. For this reason, equipment qualification is becoming of increasing importance in the field of analysis. Here, constructive cooperation between the manufacturer and the user plays an important role, as only an exact knowledge of the demands to be placed on a piece of analytical equipment can help manufacturers to avoid urmecessary development costs and enable them at the same time to undertake work in the area of qualification of the equipment. 

A validation team member from the Production department is responsible to participate in performing the validation steps during manufacturing processes and equipment qualification. This department should prepare the necessary SOPs for the new process or equipment and assist in the collection of validation data. 

Procedures must be developed and staffing provided for the collection of data that proves that the processes and equipment meet all parameters claimed.f Systems should be in place for equipment qualifications, validation, changes, and replacement. The manufacturing process validation could be invalidated without proper documentation of equipment maintenance. A minimum of three consecutive manufacturing lots should be evaluated for process validation. Parameters involved in process validation include in-process and final bulk product test, deviation analysis of the process, stability testing of final product and equipment qualification and validation. Other validation requirements are discussed by Sawyer and Stats,... 

Equipment intended to be used for critical manufacturing or control operations is subject to installation and operational qualification. Equipment qualification is documented. 

Some medical device manufacturers are confused with the requirements for an equipment performance qualification (PQ). In general, a PQ is not required for manufacturing equipment if its performance is demonstrated during process validation (PV) where the equipment must be shown to perform under the unique conditions of every product (or range of products). A separate equipment PQ is only required when it is used in a manufacturing support role, which typically includes compressed air systems, clean rooms, and purified water systems. 

While a non-GMP plant is ready for operation directly after completion of commissioning, for a GMP plant it will take another 6-12 months to establish operational readiness due to facility and equipment qualification and process validation requirements. In addition, for commercial GMP manufacture, and depending on the target markets, the facility needs to be approved by national and international health authorities. 

Defined maintenance procedures should include model or manufacturer specifics and a list of parts to be inspected, cleaned, lubricated, replaced, and/or calibrated. The replacement part numbers, cleaning solutions and lubricants, and calibration standards, along with the manufacturer s maintenance procedures to be followed, should be specified. Documentation is easily managed by creating a one-page checklist of instructions or performance parameters that can be checked off as each task is completed. Any issues or comments can be captured directly on the checklist. Provisions for failure or out-of-tolerance notification need to be clearly defined, as the equipment cannot be put back into service until the performance has been verified by conducting a performance qualification. 

An organized document filing system must be maintained. This could be a paper file, an electronic document file, or a mixture of both. The equipment inventory system contains key information on the components of each system, their performance criteria and maintenance and calibration status. All documents including installation and performance documentation, as with other documents necessary to demonstrate the quality of the data, include SOPs for the qualification procedures, calibration, maintenance, personnel training, etc. If the manufacturer s operating, service, or maintenance manuals are used or cited in the operating procedures, copies of these manuals should be maintained. To facilitate retrieval, documentation should be stored in a central location and be indexed for easy retrieval. 

Performance qualification Demonstration that equipment/processes operate satisfactorily and consistently during the manufacture of actual product... 

Thus, while a well-maintained instrument is important for any chemical/physical measurement, in NIR, without a concurrent standard for comparison, it is critical that the instrument be continuously calibrated and maintained. Since the major manufacturers of equipment have worked with the pharmaceutical industry, this has been formalized into what is called IQ/OQ/PQ, or Instrument Qualification, Operational Qualification, and Performance Qualification. The first is routinely performed (at first) by the manufacturer in the lab/process location, the second in situ by the user with help from the manufacturer, and the third is product/use dependent. These formal tests apply to all instruments in any industry. 

Instrument qualifications are the tests that are performed after the equipment is installed for use in a laboratory. Instrument qualifications include installation qualification, operational qualification, and performance qualification. These tests verify that the equipment is installed, operates, and performs according to the manufacturer s specifications. Each of these types of qualifications is defined in more detail in the following sections. 

Equipment manufacturers are faced with the challenge of qualifying all the functionality of complex equipment at the customer s lab while keeping the costs at a reasonable level. There is an expectation that the cost to qualify laboratory instrumentation be only a small fraction of the cost of the equipment itself. However, there are costs associated with both developing the qualification protocols and executing the qualification protocols. 

It is often the case that laboratories combine the use of equipment from more than one manufacturer into systems that need to be qualified. Each individual device must be qualified for the functionality of that device. Sometimes one manufacturer will sell and qualify other manufacturers devices that connect to their equipment. In this case, one company is responsible for the instrument qualifications of the entire integrated system. It is usually required that each manufacturer qualify its own device, and that following the qualification of the individual devices, the manufacturer that supplies the interface must then qualify the interfaces between the devices. 

Instrument qualifications should be executed on a scheduled basis that can be determined with the help of manufacturer s recommendations. Automated dissolution systems that are used regularly are typically re-qualified every six months to one year. Re-qualification is also recommended for other reasons including moving equipment or replacing parts. Below is a typical system re-qualification policy. 

When equipment is physically moved to another location. Definition of another location must be made within the company s SOP. Manufacturer recommends a re-qualification if equipment is lifted during the move or if the environmental conditions are different in the new location. 

---